The basic objective of this research program is to gain specific information about the mechanisms of radiation carcinogenesis using in vitro assay system. Previous results indicate that X-ray transformation in vitro can be thought of as involving at least two steps: 1) the fixation of the transformed state (presumably irreversible DNA damage) and 2) its subsequent expression in terms of morphologically altered cells. We will investigate in detail the conditions necessary for fixation and ultimate expression of the cellular damage induced by ultraviolet light and ionizing radiation which results in malignant transformation of cells. In particular, we plan to study the role that DNA repair processes play in radiation-induced transformation and the interactions between radiation and chemical agents in malignant transformation. At present, little information is available on the interactions between radiation and other agents from in vivo carcinogenesis studies or in vitro transformation work, although human populations are continually being exposed to a variety of carcinogenic agents as well as to other agents that can influence carcinogenesis. The cell system we will use is an established mouse embryo cell line which has been used for several years in this laboratory for radiation transformation experiments and is particularly appropriate for studying interactions between radiation and chemical agents. The specific chemical agents we wish to study have known interactive effects on carcinogenesis in vivo; studies in an in vitro system in which cell proliferation and other environmental conditions can be precisely controlled should yield further information about the mechanisms of carcinogenesis.